tbuckley/cabot-search huggingface dataset:
Outcomes of Endoscopic Endonasal Dacryocystorhinostomy in Glaucoma Patients
Authors: Francesco Giombi, Alessandra Di Maria, Elena Russo, Fabio Ferreli, Francesca Pirola, Francesco Giombi, Gian Marco Pace, Gianmarco Giunta, Giovanna Muci, Giuseppe Mercante, Giuseppe Spriano, Luca Malvezzi, Paolo Vinciguerra
Journal: International Journal of Surgery (2023)

Purpose: Glaucoma has been investigated on producing fibrotic changes on the conjunctival surface, undermining the functioning of the upper lacrimal drainage system. The aim of the study was to assess whether these effects may impair the effectiveness of dacryocystorhinostomy (DCR) in patients affected by both glaucoma and nasolacrimal duct obstructions (NLDO). Methods: Single-center observational retrospective study on endoscopic endonasal-DCR (EE-DCR) via posterior approach. Consecutive patients were enrolled in 2020–2023 and evaluated with proper questionnaires; resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score). Results: 17 patients (29 operated sides) were enrolled. Preoperatively, 92.1% (n = 27/29) presented severe (Munk 3-4) epiphora and 69.0% (n = 20/29) recurrent dacryocystitis. At T1, 51.72% (n = 15/29) referred residual epiphora (Munk  1) and 17.20% (n = 5/29) dacryocystitis. At T2, 34.5% (n = 10/29) still complained epiphora (Munk  1) and 6.9% (n = 2/29) symptoms of dacryocystitis. Difference of outcomes at aggregate and paired timepoints (except for T1 versus T2) resulted statistically significant (p&lt;0.05). At T2, 20 (69.0%) complete, 7 (24.2%) anatomical successes and 2 surgical failures (6.8%) were observed. Conclusion: EE-DCR in patients affected by both glaucoma and NLDO guaranteed high rates of clinical relief from epiphora and remarkable decreases in the rates of recurrent dacryocystitis, appearing as a reasonable therapeutical strategy to improve disease-related quality of life.
Correctional staff knowledge, attitudes and behaviors toward incarcerated trans people: A scoping review of an emerging literature
Authors: Kirstie Daken, Tarra Excell, Kirsty A. Clark, Jaclyn M. W. Hughto, Tait Sanders, Joseph Debattista, Carol du Plessis, Amy B. Mullens, Tania M. Phillips, Jessica Gildersleeve, Annette Brömdal
Journal: International Journal of Transgender Health (2023)

Background: Trans people are incarcerated at disproportionately high rates relative to cisgender people and are at increased risk of negative experiences while incarcerated, including poor mental health, violence, sexual abuse, dismissal of self-identity, including poor access to healthcare.
Microenvironmental network of clonal CXCL13+CD4+ T cells and Tregs in pemphigus chronic blisters
Authors: Dawoon Han, A Yeong Lee, Taehee Kim, Ji Young Choi, Mi Yeon Cho, Ahreum Song, Changhyeon Kim, Joon Ho Shim, Hyun Je Kim, Honesty Kim, Hillary Blaize D’Angio, Ryan Preska, Aaron T. Mayer, Miri Kim, Eun-Ji Choi, Tae-Gyun Kim, Eui-Cheol Shin, Kyemyung Park, Do-Young Kim, Soo-Chan Kim, Jong Hoon Kim
Journal: Journal of Clinical Investigation (2023)

BACKGROUNDPemphigus, a rare autoimmune bullous disease mediated by antidesmoglein autoantibodies, can be controlled with systemic medication like rituximab and high-dose systemic corticosteroids combined with immunosuppressants. However, some patients continue to experience chronically recurrent blisters in a specific area and require long-term maintenance systemic therapy.METHODSSkin with chronic blisters was obtained from patients with pemphigus. Immunologic properties of the skin were analyzed by immunofluorescence staining, bulk and single-cell RNA and TCR sequencing, and a highly multiplex imaging technique known as CO-Detection by indEXing (CODEX). Functional analyses were performed by flow cytometry and bulk RNA-Seq using peripheral blood from healthy donors. Intralesional corticosteroid was injected into patient skin, and changes in chronically recurrent blisters were observed.RESULTSWe demonstrated the presence of skin tertiary lymphoid structures (TLSs) with desmoglein-specific B cells in chronic blisters from patients with pemphigus. In the skin TLSs, CD4+ T cells predominantly produced CXCL13. These clonally expanded CXCL13+CD4+ T cells exhibited features of activated Th1-like cells and downregulated genes associated with T cell receptor-mediated signaling. Tregs are in direct contact with CXCL13+CD4+ memory T cells and increased CXCL13 production of CD4+ T cells through IL-2 consumption and TGF-β stimulation. Finally, intralesional corticosteroid injection improved chronic blisters and reduced skin TLSs in patients with pemphigus.CONCLUSIONThrough this study we conclude that skin TLSs are associated with the persistence of chronically recurrent blisters in patients with pemphigus, and the microenvironmental network involving CXCL13+CD4+ T cells and Tregs within these structures plays an important role in CXCL13 production.TRIAL REGISTRATIONClinicalTrials.gov NCT04509570.FUNDINGThis work was supported by National Research Foundation of South Korea (NRF-2021R1C1C1007179) and Korea Drug Development Fund, which is funded by Ministry of Science and ICT; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare (grant RS-2022-00165917).
Bone-derived PDGF-BB drives brain vascular calcification in male mice
Authors: Jiekang Wang, Ching-Lien Fang, Kathleen Noller, Zhiliang Wei, Guanqiao Liu, Ke Shen, Kangping Song, Xu Cao, Mei Wan
Journal: Journal of Clinical Investigation (2023)

Brain vascular calcification is a prevalent age-related condition often accompanying neurodegenerative and neuroinflammatory diseases. The pathogenesis of large-vessel calcifications in peripheral tissue is well studied, but microvascular calcification in the brain remains poorly understood. Here, we report that elevated platelet-derived growth factor BB (PDGF-BB) from bone preosteoclasts contributed to cerebrovascular calcification in male mice. Aged male mice had higher serum PDGF-BB levels and a higher incidence of brain calcification compared with young mice, mainly in the thalamus. Transgenic mice with preosteoclast-specific Pdgfb overexpression exhibited elevated serum PDGF-BB levels and recapitulated age-associated thalamic calcification. Conversely, mice with preosteoclast-specific Pdgfb deletion displayed diminished age-associated thalamic calcification. In an ex vivo cerebral microvascular culture system, PDGF-BB dose-dependently promoted vascular calcification. Analysis of osteogenic gene array and single-cell RNA-Seq (scRNA-Seq) revealed that PDGF-BB upregulated multiple osteogenic differentiation genes and the phosphate transporter Slc20a1 in cerebral microvessels. Mechanistically, PDGF-BB stimulated the phosphorylation of its receptor PDGFRβ (p-PDGFRβ) and ERK (p-ERK), leading to the activation of RUNX2. This activation, in turn, induced the transcription of osteoblast differentiation genes in PCs and upregulated Slc20a1 in astrocytes. Thus, bone-derived PDGF-BB induced brain vascular calcification by activating the p-PDGFRβ/p-ERK/RUNX2 signaling cascade in cerebrovascular cells.
Cancer cell-intrinsic mechanisms driving acquired immune tolerance
Authors: Ehsan Ghorani, Charles Swanton, Sergio A. Quezada
Journal: Immunity (2023)

Immune evasion is a hallmark of cancer, enabling tumors to survive contact with the host immune system and evade the cycle of immune recognition and destruction. Here, we review the current understanding of the cancer cell-intrinsic factors driving immune evasion. We focus on T cells as key effectors of anti-cancer immunity and argue that cancer cells evade immune destruction by gaining control over pathways that usually serve to maintain physiological tolerance to self. Using this framework, we place recent mechanistic advances in the understanding of cancer immune evasion into broad categories of control over T cell localization, antigen recognition, and acquisition of optimal effector function. We discuss the redundancy in the pathways involved and identify knowledge gaps that must be overcome to better target immune evasion, including the need for better, routinely available tools that incorporate the growing understanding of evasion mechanisms to stratify patients for therapy and trials.
Thermal ablation after endoscopic mucosal resection of large colorectal polyps: not only the margins, but also the base?
Authors: Roupen Djinbachian, Heiko Pohl, Douglas K Rex, John M Levenick, Douglas K Pleskow, Michael B Wallace, Mouen Khashab, Ajaypal Singh, Joshua Melson, Dennis Yang, Aleksandar Gavrić, Daniel von Renteln
Journal: Gut (2023)
Impact of Mycobacterium tuberculosis strain type on multidrug-resistant tuberculosis severity, Republic of Moldova
Authors: Elena Chesov, Dumitru Chesov, Maja Reimann, Viola Dreyer, Christian Utpatel, Matthias I. Gröschel, Nelly Ciobanu, Valeriu Crudu, Christoph Lange, Jan Heyckendorf, Matthias Merker
Journal: Journal of Infection (2023)
Assessing Metabolic Differences Associated with Exposure to Polybrominated Biphenyl and Polychlorinated Biphenyls in the Michigan PBB Registry
Authors: Susan S. Hoffman, Donghai Liang, Robert B. Hood, Youran Tan, Metrecia L. Terrell, M. Elizabeth Marder, Hillary Barton, Melanie A. Pearson, Douglas I. Walker, Dana Boyd Barr, Dean P. Jones, Michele Marcus
Journal: Environmental Health Perspectives (2023)

Background: Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. Objectives: In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. Methods: HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB in utero or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and ΣPCB (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. Results: Mean levels were 1.75 ng/mL [standard deviation (SD): 13.9] for PBB-153 and 1.04 ng/mL (SD: 0.788) for ΣPCB. Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) p&lt;0.2], respectively. There were 2,861 features associated with ΣPCB (FDR p&lt;0.2). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with ΣPCB in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with ΣPCB levels (level 1 evidence). Conclusions: Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that ΣPCB was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657
British Society of Gastroenterology guidelines on sedation in gastrointestinal endoscopy
Authors: Reena Sidhu, David Turnbull, Hasan Haboubi, John S Leeds, Chris Healey, Srisha Hebbar, Paul Collins, Wendy Jones, Mohammad Farhad Peerally, Sara Brogden, Laura J Neilson, Manu Nayar, Jacqui Gath, Graham Foulkes, Nigel J Trudgill, Ian Penman
Journal: Gut (2023)

Over 2.5 million gastrointestinal endoscopic procedures are carried out in the United Kingdom (UK) every year. Procedures are carried out with local anaesthetic r with sedation. Sedation is commonly used for gastrointestinal endoscopy, but the type and amount of sedation administered is influenced by the complexity and nature of the procedure and patient factors. The elective and emergency nature of endoscopy procedures and local resources also have a significant impact on the delivery of sedation. In the UK, the vast majority of sedated procedures are carried out using benzodiazepines, with or without opiates, whereas deeper sedation using propofol or general anaesthetic requires the involvement of an anaesthetic team. Patients undergoing gastrointestinal endoscopy need to have good understanding of the options for sedation, including the option for no sedation and alternatives, balancing the intended aims of the procedure and reducing the risk of complications. These guidelines were commissioned by the British Society of Gastroenterology (BSG) Endoscopy Committee with input from major stakeholders, to provide a detailed update, incorporating recent advances in sedation for gastrointestinal endoscopy. This guideline covers aspects from pre-assessment of the elective ‘well’ patient to patients with significant comorbidity requiring emergency procedures. Types of sedation are discussed, procedure and room requirements and the recovery period, providing guidance to enhance safety and minimise complications. These guidelines are intended to inform practising clinicians and all staff involved in the delivery of gastrointestinal endoscopy with an expectation that this guideline will be revised in 5-years’ time.
Increased risk of severe generalized pustular psoriasis due to tuberculosis screening delay for spesolimab initiation
Authors: Madison Hackley, Daphne Thampy, Shayan Waseh, Steven R. Feldman, Andrew Blauvelt, Jeffrey M. Weinberg, Sergio Schwartzman, Wilson Liao, Ronald Prussick, Jeffrey M. Cohen, Sylvia Hsu, Dafna D. Gladman, Soumya Reddy, Joseph Merola, Cassandra Calabrese, Mark Lebwohl, Chesahna Kindred, Lauren Miller, Leon Kircik, Clive Liu, G. Michael Lewitt, Lara Wine Lee, Seemal Desai, Abby Van Voorhees, Brad P. Glick, Jennifer Soung
Journal: Journal of the American Academy of Dermatology (2023)
The limitation of flowcytometry is ignored in the assessment of antimitochondrial antibodies in rheumatoid arthritis: comment on the article by Moore et al
Authors: La‐He Jearn, Think‐You Kim
Journal: Arthritis & Rheumatology (2023)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Down‐regulation of Lon protease 1 lysine crotonylation aggravates mitochondrial dysfunction in polycystic ovary syndrome
Authors: Yuan Xie, Shuwen Chen, Zaixin Guo, Ying Tian, Xinyu Hong, Penghui Feng, Qiu Xie, Qi Yu
Journal: MedComm (2023)

Polycystic ovary syndrome (PCOS) is a prevalent reproductive endocrine disorder, with metabolic abnormalities and ovulation disorders. The post-translational modifications (PTMs) are functionally relevant and strengthen the link between metabolism and cellular functions. Lysine crotonylation is a newly identified PTM, the function of which in PCOS has not yet been reported. To explore the molecular mechanisms of crotonylation involved in the abnormalities of metabolic homeostasis and oocyte maturation in PCOS, by using liquid chromatography-tandem mass spectrometry analysis, we constructed a comprehensive map of crotonylation modifications in ovarian tissue of PCOS-like mouse model established by dehydroepiandrosterone induction. The crotonylation levels of proteins involved in metabolic processes were significantly decreased in PCOS ovaries compared to control samples. Further investigation showed that decrotonylation of Lon protease 1 (LONP1) at lysine 390 was associated with mitochondrial dysfunction in PCOS. Moreover, LONP1 crotonylation levels in PCOS were correlated with ovarian tissue oxidative stress levels, androgen levels, and oocyte development. Consistently, down-regulation of LONP1 and LONP1 crotonylation levels were also observed in the blood samples of PCOS patients. Collectively, our study revealed a mechanism by which the decrotonylation of LONP1 may attenuate its activity and alter follicular microenvironment to affect oocyte maturation in PCOS.
MRP1-Dependent Extracellular Release of Glutathione Induces Cardiomyocyte Ferroptosis After Ischemia-Reperfusion
Authors: Genki Ichihara, Yoshinori Katsumata, Yuki Sugiura, Yuta Matsuoka, Rae Maeda, Jin Endo, Atsushi Anzai, Kohsuke Shirakawa, Hidenori Moriyama, Hiroki Kitakata, Takahiro Hiraide, Shinichi Goto, Seien Ko, Yuji Iwasawa, Kazuhisa Sugai, Kyohei Daigo, Shinya Goto, Kazuki Sato, Ken-ichi Yamada, Makoto Suematsu, Masaki Ieda, Motoaki Sano
Journal: Circulation Research (2023)

The membrane components of cardiomyocytes are rich in polyunsaturated fatty acids, which are easily oxidized. Thus, an efficient glutathione-based lipid redox system is essential for maintaining cellular functions. However, the relationship between disruption of the redox system during ischemia-reperfusion (IR), oxidized lipid production, and consequent cell death (ferroptosis) remains unclear. We investigated the mechanisms underlying the disruption of the glutathione-mediated reduction system related to ferroptosis during IR and developed intervention strategies to suppress ferroptosis.
The alpha-adrenergic antagonist prazosin promotes cytosolic siRNA delivery from lysosomal compartments
Authors: Thijs Van de Vyver, Cristina Muntean, Iuliia Efimova, Dmitri V. Krysko, Lynn De Backer, Stefaan C. De Smedt, Koen Raemdonck
Journal: Journal of Controlled Release (2023)
H3K27M Mutant Glioma: Disease Definition and Biological Underpinnings
Authors: Amanda M Saratsis, Truman Knowles, Antonela Petrovic, Javad Nazarian
Journal: Neuro-Oncology (2023)

Abstract High-grade glioma (HGG) is the most common cause of cancer death in children and the most common primary central nervous system tumor in adults. While pediatric HGG was once thought to be biologically similar to the adult form of disease, research has shown these malignancies to be significantly molecularly distinct, necessitating distinct approaches to their clinical management. However, emerging data have shown shared molecular events in pediatric and adult HGG including the histone H3K27M mutation. This somatic missense mutation occurs in genes encoding one of two isoforms of the Histone H3 protein, H3F3A (H3.3), or HIST1H3B (H3.1), and is detected in up to 80% of pediatric diffuse midline gliomas and in up to 60% of adult diffuse gliomas. Importantly, the H3K27M mutation is associated with poorer overall survival and response to therapy compared to patients with H3 wild-type tumors. Here, we review the clinical features and biological underpinnings of pediatric and adult H3K27M mutant glioma, offering a groundwork for understanding current research and clinical approaches for the care of patients suffering with this challenging disease.
Inflammasome: structure, biological functions, and therapeutic targets
Authors: Yali Dai, Jing Zhou, Chunmeng Shi
Journal: MedComm (2023)

Inflammasomes are a group of protein complex located in cytoplasm and assemble in response to a wide variety of pathogen-associated molecule patterns, damage-associated molecule patterns, and cellular stress. Generally, the activation of inflammasomes will lead to maturation of proinflammatory cytokines and pyroptotic cell death, both associated with inflammatory cascade amplification. A sensor protein, an adaptor, and a procaspase protein interact through their functional domains and compose one subunit of inflammasome complex. Under physiological conditions, inflammasome functions against pathogen infection and endogenous dangers including mtROS, mtDNA, and so on, while dysregulation of its activation can lead to unwanted results. In recent years, advances have been made to clarify the mechanisms of inflammasome activation, the structural details of them and their functions (negative/positive) in multiple disease models in both animal models and human. The wide range of the stimuli makes the function of inflammasome diverse and complex. Here, we review the structure, biological functions, and therapeutic targets of inflammasomes, while highlight NLRP3, NLRC4, and AIM2 inflammasomes, which are the most well studied. In conclusion, this review focuses on the activation process, biological functions, and structure of the most well-studied inflammasomes, summarizing and predicting approaches for disease treatment and prevention with inflammasome as a target. We aim to provide fresh insight into new solutions to the challenges in this field.
Immune-depleted tumor microenvironment is associated with poor outcomes and BTK inhibitor resistance in mantle cell lymphoma
Authors: Preetesh Jain, Krystle Nomie, Nikita Kotlov, VitaIy Segodin, Holly Hill, Chi Young Ok, Ahmed Fetooh, Rashmi Kanagal-Shamanna, Francisco Vega, Alexander Bagaev, Nathan Fowler, Christopher R. Flowers, Michael Wang
Journal: Blood Cancer Journal (2023)
Mpox neutralising antibodies at 6 months from mpox infection or MVA-BN vaccination: a comparative analysis
Authors: Nicolò Moschetta, Angelo Roberto Raccagni, Micol Bianchi, Sara Diotallevi, Riccardo Lolatto, Caterina Candela, Caterina Uberti Foppa, Maria Rita Gismondo, Antonella Castagna, Silvia Nozza, Davide Mileto
Journal: The Lancet Infectious Diseases (2023)